1. Field of the Invention
The present invention relates to a method for preparing leucocyte-free blood preparation and to a blood administration set.
2. Description of the Related Art
It has been known that upon transfusion of various blood preparations such as erythrocyte concentrate and platelet preparation, various side effects attributable to leucocytes mixed in the preparation occur, examples of which include fever, chill, headache, urticaria, arthralgia, blood pressure depression (hypotension), dyspnea, anaphylactic shock and so on. To prevent such defects accompanying transfusion, there has been generally used a leucocyte removal filter mainly having a porous filter membrane material such as polyester, nonwoven fabric and polyurethane.
In the leucocyte removal filter, in spite of improvements in the filter membrane material, severe cases such as abrupt hypotension and shock symptom upon use have been reported (Pharmaceuticals and Medical Devices Safety Information, No. 150 (October 1998), Agency of Countermeasures for the Safety of Medicines, Ministry of Health and Welfare, p. 2-5). Accordingly, investigation of the cause of the occurrence of such side effects and establishment of countermeasures for improvement have been important issues.
Meanwhile it has been pointed out that the occurrence of side effects when leucocyte removal filters are used is caused by the participation of bradykinin and so on (S. Ito, et al., The Journal of Japan Society for Clinical Anethesia, 19 [6] (1999) p.414-418), the induction of anaphylaxis reaction due to an increase in concentration of kinin-related substances in blood (A. Hamaguchi, Biomedicine and Therapeutics, 33[1] (1999) p.74), mass production of interleukin-4 (Noguchi, M. et al., Therapeutic Apheresis, 2[2] (1998), p.109-114) and the like.
However, when leucocyte removal filters are used, side effects such as acute hypotension and severe shock symptom may occur. Therefore, they are not fully explained by the participation of bradykinin and so on as described above or the like, and safety countermeasures for preventing side effects from occurring have not been established yet.
Therefore, there has been an increasing demand for the clarification of the causes of side effects such as hypotension and establishment of safety countermeasures for preventing the side effects from occurring.
An object of the present invention is to provide a method for preparing a leucocyte-free blood preparation that can avoid side effects that would otherwise occur when transfusion is performed using a leucocyte removal filter so that it is highly safe and that is simple and easy.
Another object of the present invention is to provide a blood administration set that can avoid side effects that would otherwise occur when transfusion is performed using a leucocyte removal filter so that it is highly safe and that can be used simply and easily.
The present inventors have made extensive study in order to achieve the above-mentioned objects. As a result, they have found out the main causative substance of side effects such as hypotension that occur when transfusion is performed using a leucocyte removal filter and further that removal of the blood component containing the causative substance to outside the system can improve the safety at the time of transfusion. The present invention has been achieved based on this discovery.
With a view to elucidate the cause of occurrence of side effects at the time of transfusion of a leucocyte-free blood preparation (hereinafter sometimes referred to simply as xe2x80x9cblood preparationxe2x80x9d) using a leucocyte removal filter, the present inventors have made analysis of gaseous components in a blood preparation by a nitrogen oxide (hereinafter referred to also as xe2x80x9cNOxe2x80x9d) electrode (E. Murakami, Tissue Culture Engineering, 25 (1999), p.162-163) and an oxygen electrode provided upstream and downstream of a leucocyte removal filter.
FIG. 1 is a schematic illustration of an apparatus used for the analysis of gaseous components in the blood preparation as described above. A leucocyte removal filter 1 is communicated with a blood bag 100 upstream thereof through a connection tube 9. The leucocyte removal filter 1 is connected with a drip chamber 4 through a connection tube 8 and a drip port 5, which is an end portion of the connection tube 8, is open inside the drip chamber 4. Downstream of the drip chamber 4 is connected a connection tube 7 provided with a clamp 6. The leucocyte removal filter 1 and the connection tube 9 upstream thereof are provided with air vents 2 and 3, respectively.
In the above apparatus, NO electrodes 10 and 12 and oxygen electrodes 11 and 13 are provided in the passages upstream and downstream of the leucocyte removal filter 1 so that the electrodes contact the liquid. The electrodes are connected to measurement apparatuses (not shown), respectively. A leucocyte containing liquid was introduced and NO concentrations and oxygen partial pressures in the liquid before and after passing the leucocyte removal filter 1 were continuously measured. Further, the blood components after passing the leucocyte removal filter 1 were administered intravenously to an animal (rabbit) and the influence thereof on blood pressure was observed.
As a result, it has been found out that among the blood components after passing the leucocyte removal filter 1, the first fraction (effluent in the first stage of filtration) tends to have considerably high NO concentration and low oxygen partial pressure, and causes hypotension.
Therefore, the present invention has been achieved based on this findings.
That is, the present invention provides a method for preparing a leucocyte-free blood preparation comprising the steps of: introducing a leucocyte containing liquid into a leucocyte removal filter; removing a first fraction from an effluent that is discharged from the leucocyte removal filter; and obtaining an effluent portion that is discharged after the first fraction as a leucocyte-free blood preparation.
Also, the present invention provides a blood administration set comprising: a leucocyte removal filter having an inlet port for introducing a leucocyte containing liquid, for separating leucocytes from the leucocyte containing liquid; and a passage for discharging a leucocyte-free blood preparation from the leucocyte removal filter; wherein the passage comprises a device for removing a first fraction from an effluent discharged from the leucocyte removal filter.
According to a preferred embodiment, the present invention provides a blood administration set as described above, wherein the device for removing the first fraction comprises: a cylindrical casing; an inlet port provided upstream of the casing communicated with the leucocyte removal filter; an outlet port provided downstream of the casing; and a tube provided inside the casing, having one end that is liquid-tightly bonded to the casing so as to open in the outlet port of the casing and the other end that extends to a predetermined position at an interval of a first space toward the inlet port of the casing, an inner wall of the casing and an outer wall of the tube defining a second space for pooling a liquid; and preferably an absorbent provided in the second space.
According to another preferred embodiment, the present invention provides a blood administration set as described, wherein the device for removing the first fraction comprises: a cylindrical casing; an inlet port provided upstream of the casing communicated with the leucocyte removal filter; an outlet port provided downstream of the casing; a tube provided inside the casing, having one end that is liquid-tightly bonded to the casing so as to open in the inlet port of the casing and the other end that extends to a predetermined position at an interval of a first space toward the outlet port of the casing, an inner wall of the casing and an outer wall of the tube defining a second space for pooling a liquid; and an absorbent provided in the second space.
According to a still another preferred embodiment, the present invention provides a blood administration set as described above, wherein the device for removing the first fraction comprises: a branched tube having an inlet tube communicated with the leucocyte removal filter, a first branch and a second branch communicated with the inlet tube; and a clamp provided downstream of the first branch; and preferably a connection tube communicated with the second branch; a bag communicated with the connection tube; and a clamp provided with the connection tube.
According to a yet another preferred embodiment, the present invention provides a blood administration set as described above, wherein the device for removing the first fraction comprises: a two-way cock having an inlet port communicated with the leucocyte removal filter, a first outlet port, and a second outlet port; and preferably a connection tube communicated with the second outlet port; and a bag communicated with the connection tube.
According to the method of preparing a leucocyte-free blood preparation according to the present invention, side effects that would otherwise occur when transfusion is performed using a leucocyte removal filter can be avoided so that it is very highly safe. Furthermore, the method for preparing a leucocyte-free blood preparation according to the present invention is simple and easy. For these reasons, the method for preparing a leucocyte-free blood preparation according to the present invention is very useful.
The blood administration set of the present invention can be preferably used in the method for preparing a leucocyte-free blood preparation according to the present invention. Furthermore, the blood administration set of the present invention can be used simply and easily. For these reasons, the blood administration set of the present invention is very useful.